Cadherins mediate cocaine-induced synaptic plasticity and behavioral conditioning

Nat Neurosci. 2017 Apr;20(4):540-549. doi: 10.1038/nn.4503. Epub 2017 Feb 13.


Drugs of abuse alter synaptic connections in the reward circuitry of the brain, which leads to long-lasting behavioral changes that underlie addiction. Here we show that cadherin adhesion molecules play a critical role in mediating synaptic plasticity and behavioral changes driven by cocaine. We demonstrate that cadherin is essential for long-term potentiation in the ventral tegmental area and is recruited to the synaptic membranes of excitatory synapses onto dopaminergic neurons following cocaine-mediated behavioral conditioning. Furthermore, we show that stabilization of cadherin at the membrane of these synapses blocks cocaine-induced synaptic plasticity, leading to a reduction in conditioned place preference induced by cocaine. Our findings identify cadherins and associated molecules as targets of interest for understanding pathological plasticity associated with addiction.

MeSH terms

  • Animals
  • Cadherins / metabolism
  • Cadherins / physiology*
  • Cocaine / pharmacology*
  • Conditioning, Psychological / physiology*
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / physiology
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology
  • Male
  • Mice
  • Mice, Transgenic
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Receptors, AMPA / metabolism
  • Synapses / physiology
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / metabolism
  • Ventral Tegmental Area / physiology*


  • Cadherins
  • Receptors, AMPA
  • Cocaine
  • glutamate receptor ionotropic, AMPA 1